title: Biological subtypes of triple-negative breast cancer are associated with distinct morphological changes and clinical behaviour.
abstract: Triple negative breast cancer (TNBC) is a heterogeneous group of tumours accounting for approximately 10-20% of all breast carcinomas. To identify biologically distinct subgroups of TNBC and to assess their clinical properties we examined a series of 142 consecutive patients all of which had received adjuvant cytotoxic chemotherapy using a comprehensive panel of immunostains. Hierarchical unsupervised cluster analysis based on the expression of 13 markers permitted separation of four distinct groups (basal A, basal B, basoluminal, luminal) with the main distinguishing features being cytokeratin (Ck5/6, Ck14, Ck19), EGFR, p53, p16, and Ki-67 expression. Clusters differed with respect to patient age, modified Bloom and Richardson grading, the presence of tumour necrosis, growth pattern and survival, both in uni- and multivariate analysis. Basal (A or B) tumours showed a substantially better outcome compared with basoluminal and luminal tumours. Our data underline the heterogeneity of TNBC and characterise potentially relevant biological subtypes.
authors.affiliation: Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany.
authors.forename: Zeinab
authors.initials: Z
authors.lastname: Elsawaf
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Sinn
authors.forename: Joachim
authors.initials: J
authors.lastname: Rom
authors.forename: Justo Lorenzo
authors.initials: JL
authors.lastname: Bermejo
authors.forename: Andreas
authors.initials: A
authors.lastname: Schneeweiss
authors.forename: Sebastian
authors.initials: S
authors.lastname: Aulmann
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D016000:Cluster Analysis; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D006801:Humans; D053556:Keratin-1 / Q000032:analysis; D053547:Keratin-14 / Q000032:analysis; D053555:Keratin-5 / Q000032:analysis; D019394:Ki-67 Antigen / Q000032:analysis; D008875:Middle Aged; D009336:Necrosis; D060787:Neoplasm Grading; D016016:Proportional Hazards Models; D064726:Triple Negative Breast Neoplasms / Q000737:chemistry / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D053556:Keratin-1; D053547:Keratin-14; D053555:Keratin-5; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; D066246:ErbB Receptors
keywords: Breast cancer; Cluster analysis; Immunohistochemistry; Survival; Triple negative